Schäfer-Korting M, Kirch W, Axthelm T, Köhler H, Mutschler E
Clin Pharmacol Ther. 1983 Mar;33(3):283-8. doi: 10.1038/clpt.1983.34.
Atenolol kinetics were investigated in six healthy subjects after 100 mg orally, as monotherapy a 6-day treatment began 48 hr later. After a therapy-free interval of 4 wk, the same subjects received the same dose of atenolol with 1 gm ampicillin, 500 mg aspirin, and with 300 mg allopurinol. Allopurinol and aspirin did not substantially alter the kinetics of atenolol. After a single oral dose of 100 mg atenolol combined with 1 gm ampicillin, the bioavailability of atenolol was reduced to 36 +/- 5% compared to 60 +/- 8% after monotherapy. During long-term treatment with atenolol and ampicillin the bioavailability of atenolol fell to 24% (P less than 0.01). Mean peak plasma levels were lowered from 511 +/- 59 ng/ml on monotherapy to 344 +/- 33 ng/ml after the combination with ampicillin. The area under the plasma level-time curve, mean steady-state concentration, and urinary recovery were reduced, also. Twelve hours after 100 mg atenolol and 1 gm ampicillin, exercise tachycardia was significantly higher than after atenolol alone. During the 4-wk treatment in six hypertensive patients blood pressure levels of those on atenolol alone were not different from those on the combination therapy with ampicillin.
对6名健康受试者口服100毫克阿替洛尔后的动力学进行了研究,单一疗法于48小时后开始为期6天的治疗。在4周的无治疗间隔期后,相同受试者接受相同剂量的阿替洛尔,并分别联合1克氨苄西林、500毫克阿司匹林和300毫克别嘌醇。别嘌醇和阿司匹林并未显著改变阿替洛尔的动力学。单次口服100毫克阿替洛尔联合1克氨苄西林后,阿替洛尔的生物利用度降至36±5%,而单一疗法后为60±8%。在阿替洛尔和氨苄西林的长期治疗期间,阿替洛尔的生物利用度降至24%(P<0.01)。平均血浆峰值水平从单一疗法时的511±59纳克/毫升降至联合氨苄西林后的344±33纳克/毫升。血浆水平-时间曲线下面积、平均稳态浓度和尿回收率也降低了。100毫克阿替洛尔和1克氨苄西林服用12小时后,运动性心动过速显著高于单独服用阿替洛尔后。在6名高血压患者的4周治疗期间,单独服用阿替洛尔患者的血压水平与联合氨苄西林治疗患者的血压水平无差异。